by Jaron Terry, APR
It’s fairly common knowledge that stress can affect health and well-being. Determining exactly how and why has been the goal of Ohio State’s Institute for Behavioral Medicine Research (IBMR) since 1996. An internationally recognized center for the study of body-mind interaction, the IBMR has attracted more than $186 million in National Institutes of Health (NIH) grants. This year, the Institute moved into its own dedicated building on The Ohio State University Medical Center campus.
Stress, with a capital S, has been the focus of numerous groundbreaking findings generated by members of the IBMR,” says Ronald Glaser, PhD, director.
“The complicated, interactive relationship between stressors – emotional and environmental – and the three body systems – immune, central nervous and endocrine – is fascinating and has garnered a great deal of attention, not only from scientists around the world, but from the general public as well,” adds Glaser, who also holds The Gilbert and Kathryn Mitchell Chair in Ohio State’s College of Medicine.
That high level of interest was the impetus for the IBMR, to coordinate, accelerate and expand the multidisciplinary, collaborative work of more than 20 Ohio State scientists and clinicians, all recognized experts in their respective fields.
A virologist, Glaser came to Ohio State in 1978 to chair what is now the Department of Molecular Virology, Immunology and Medical Genetics. He later served for two years as associate dean for Research in the College of Medicine before serving 12 years as associate vice president for Research. Having accumulated nearly three decades as a senior administrator and noted scientist, he was uniquely qualified to lead the IBMR.
Those who had been studying the mind-body connection for several years, including William Malarkey, MD, John Sheridan, PhD, and Janice Kiecolt-Glaser, PhD, were excited to find a forum for discussion and collaboration in the IBMR.
“One aspect of our teamwork that we consider responsible for our success in landing large competitive grants is that we have simultaneous human and animal model studies addressing a given issue,” notes Glaser.
One example of simultaneous human and animal model studies is a recent NIH grant that Sheridan, Glaser, Marshall Williams, PhD, and Randy Nelson, PhD, received to investigate stress effects on the ability of Epstein-Barr virus (EBV)-encoded proteins to induce inflammation and sickness behavior. The five-year study will build on prior work from Glaser’s lab that has focused on the pathophysiology of EBV, which is associated with several human cancers. With new and extensive literature linking chronic inflammation to an increased risk for cancer, a primary hypothesis of this new study is that other early viral proteins encoded by EBV and other herpes viruses will induce inflammatory cytokines.
“It is the combination of basic and clinical science such as this that gives us the breadth and depth to distinguish IBMR from other programs and allows us to construct investigations that launch our research to continually higher levels,” Glaser adds. These and other stress and cancer- related studies are part of the Cancer Control Program of Ohio State’s Comprehensive Cancer Center.
IMBR investigators study a wide spectrum of stressors and their effects on an equally wide range of health conditions in multiple specialties. The following examples are drawn from a vast portfolio of current and ongoing research projects:
“The cognitive center of our brain – the prefrontal cortex – has crosstalk with the fear center – the amygdala,” explains William Malarkey, MD, an associate director of the IBMR. Anxiety and worry cause the amygdala to influence the secretion of certain hormones, which in turn can dysregulate the immune system.
“Through an awareness process we call ‘mindful meditation’ that involves the prefrontal cortex, neuroendocrine outputs of the amygdala can be dampened. In effect, a person can ‘talk themselves down’ to improve various biological and psychological measures of health,” Malarkey adds.
Malarkey, who also directs Ohio State’s Clinical Research Center (CRC), which provides a well-controlled research environment to allow simultaneous study of multiple subjects and 24-hour sampling capabilities, recently completed an NIH-sponsored clinical trial that examined the role of mindful meditation in lowering inflammatory markers (CRP and IL-6). Conducted with colleagues Maryanna Klatt, Nicole Leenders and David Jarjoura, the study also evaluated biopsychosocial metrics. A group of 180 Ohio State faculty and staff was randomized to receive either mindful meditation training or exercise and nutrition counseling over an eight-week period and then asked to continue their program over the next year. Results will be forthcoming over the next several years.
Stress and Vaccine Effectiveness
“Psychological stressors, including social stressors, profoundly influence behavior and immunity,” says Sheridan, who is an associate director of the IBMR, associate dean of Research and professor of Oral Biology in the College of Dentistry.
He explains that in humans, chronic stress, such as caregiving for a spouse with progressive dementia, is associated with an increased prevalence of mental health complications, including anxiety and depression.
“While it is well known that stress-associated conditions significantly influence health and the quality of life, the mechanisms involved are not completely understood. However, it is well established that specific central nervous system pathways act to translate social stimuli into peripheral biological signals,” Sheridan notes.
Approximately 15 years ago, IBMR researchers designed a vaccine study to examine the effects of chronic stress on the immune response to an influenza viral vaccine. Caregivers of spouses with Alzheimer’s disease showed a poorer antibody response and virus-specific T-cell response following vaccination compared to the control subjects. Furthermore, the immunological decrements associated with the stress of caregiving are of particular concern because older individuals may already have an age-related deterioration of the immune system that is associated with poor health.
Until Stress Do Us Part
Kiecolt-Glaser, professor of Psychiatry and Psychology and holder of The S. Robert Davis Chair of Medicine in Ohio State’s College of Medicine, has been studying the biological effects of stress on marriage, among other topics, for 25 years. Her work, which has been published in numerous peer-reviewed scholarly journals, was prominently showcased in a New York Times Magazine feature article earlier this year. In one study, 90 newlywed couples were admitted to the CRC for a 24-hour period, during which detailed assessments were made of each couple’s conflict-resolution behaviors and subsequent changes in endocrine and immune function.
She and her colleagues, including Glaser and Malarkey, found that pervasive differences in endocrine and immune function are reliably associated with negative or hostile behaviors during marital conflict with women showing greater physiological changes than men. The Times article Is Marriage Good for Your Health? also discusses their follow-on study, published in The Archives of General Psychiatry, demonstrating that couples in troubled marriages experience longer wound-healing times.
Health Effects of Social Isolation
By using mouse models of cardiovascular and cerebrovascular disease to better understand how social environment impacts human health, Courtney DeVries, PhD, has found that social isolation and feelings of loneliness are associated with an increased incidence of stroke and cardiac arrest as well as reduced recovery and quality of life.
“As with humans, our data indicate, the body’s response to stroke and cardiac arrest is very different for socially isolated versus integrated mice; indeed, socially isolated mice sustain greater neuronal damage and exhibit less recovery of function after both stroke and cardiac arrest,” she says.
DeVries has demonstrated that the difference lies in the inflammatory response within the brain following loss of blood flow due to stroke or cardiac arrest; socially isolated mice exhibit greater inflammation, which can increase the extent of
brain damage. She and her colleagues believe that the proinflammatory bias contributes to the increased incidences of depression and anxiety among socially isolated patients.
“Our goals are to increase awareness of social environment as a potential risk factor in disease, and to identify the physiological mechanisms through which social environment impacts health,” DeVries adds.
Antibodies can be good or bad. Certain antibodies are helpful in fighting bacterial infections such as pneumonia; others can aggravate allergies and asthma. In an effort that will help pharmacologists develop drugs that target a certain protein (CD86) or specific group of enzymes (phosphatases), Virginia Sanders, PhD, professor and director of the Integrated Biomedical Science Graduate Program, has focused her studies on how the nervous system communicates with B lymphocytes (a type of cell that produces antibodies) to have them produce more or less.
Her laboratory discovered that the neurotransmitter norepinephrine elevates the expression of CD86 on a B lymphocyte and that engagement of CD86 activates a direct signaling pathway to increase the amount of protective antibodies made. She and her colleagues also showed that the mechanism by which norepinephrine increases the antibody count associated with allergy/asthma involves a phosphatase, which triggers other events leading to gene expression and more antibodies being made.
Ohio State’s IBMR includes faculty from five Ohio State University colleges and 12 departments and centers:
• Public Health
• Social and Behavioral Sciences
• Veterinary Medicine
Departments and Centers
• Center for Clinical and Translational Science
• Comprehensive Cancer Center
• Davis Heart and Lung Research Institute
• Internal Medicine
• Molecular Virology, Immunology and Medical Genetics
• Oral Biology
• Veterinary Pathobiology
• Ohio State’s Institute for Behavioral Medicine Research (IBMR) is an internationally recognized center for the study of body-mind interaction that has attracted more than $186 million in National Institutes of Health grants since its founding in 1996.
• The combination of basic and clinical science investigations, often simultaneously on the same topic, distinguishes Ohio State’s IBMR from other programs around the world.
• Ohio State’s IBMR includes faculty from five colleges – Dentistry, Medicine, Public Health, Social and Behavioral Sciences and Veterinary Medicine – and 12 academic departments and research centers.
from left: Ronald Glaser, PhD, William Malarkey, MD, John Sheridan, PhD, Janice Kiecolt-Glaser, PhD, and Courtney DeVries, PhD.